US 12,440,572 B2
FVIII fusion protein and use thereof
Hongsheng Su, Beijing (CN); Xiaoshan Wang, Beijing (CN); Bin Liu, Beijing (CN); Xian Chen, Beijing (CN); Xiang Li, Beijing (CN); Luyan Zhu, Beijing (CN); Shuya Wang, Kaifeng (CN); Shuang Wang, Beijing (CN); Wenwen Wang, Kaifeng (CN); Lingli Huang, Kaifeng (CN); Qilei Wang, Kaifeng (CN); Haitao Hu, Kaifeng (CN); Lili Zhang, Kaifeng (CN); Jie Gao, Kaifeng (CN); Zijia Ren, Kaifeng (CN); Chunfeng Xiao, Beijing (CN); and Yali Wang, Beijing (CN)
Assigned to ZHENGZHOU GENSCIENCES INC., Zhengzhou (CN)
Appl. No. 17/055,403
Filed by Zhengzhou Gensciences Inc., Henan (CN)
PCT Filed May 16, 2019, PCT No. PCT/CN2019/087156
§ 371(c)(1), (2) Date Nov. 13, 2020,
PCT Pub. No. WO2019/219049, PCT Pub. Date Nov. 21, 2019.
Claims priority of application No. 201810481941.X (CN), filed on May 18, 2018.
Prior Publication US 2021/0361775 A1, Nov. 25, 2021
Int. Cl. A61K 47/00 (2006.01); A61K 38/37 (2006.01); A61K 47/54 (2017.01); A61K 47/60 (2017.01); A61P 7/04 (2006.01)
CPC A61K 47/60 (2017.08) [A61K 38/37 (2013.01); A61K 47/545 (2017.08); A61P 7/04 (2018.01); C07K 2319/31 (2013.01)] 10 Claims
 
1. A polyalkylene glycol-conjugated coagulation factor VIII fusion protein, wherein the coagulation factor VIII active moiety (FVIII) is directly or indirectly linked to a fusion partner for prolonging half-life via a peptide linker to form the fusion protein, and the fusion protein is further conjugated to the polyalkylene glycol;
wherein the fusion partner is an immunoglobulin Fc fragment and the polyalkylene glycol is 40 kD branched polyethylene glycol;
the coagulation factor VIII active moiety is linked to the fusion partner via a peptide linker and the peptide linker includes a flexible peptide segment and a rigid peptide segment;
the rigid peptide segment is the carboxy terminal peptide of human chorionic gonadotropin β subunit and the rigid peptide segment comprises an amino acid sequence selected from:
 
 (i)
 
 (SEQ ID NO: 11)
 
 PRFQDSSSSKAPPPSLPSPSRLPGPSDTPILPQ;
 
 
 
 (ii)
 
 (SEQ ID NO: 12)
 
 SSSSKAPPPSLPSPSRLPGPSDTPILPQ;
 
 
 
 (iii)
 
 (SEQ ID NO: 13)
 
 SSSSKAPPPS;
 
 and
 
 
 
 (iv)
 
 (SEQ ID NO: 14)
 
 SRLPGPSDTPILPQ;
and
the flexible peptide segment has a general formula (GS)a(GGS)b(GGGS)c(GGGGS)d, where a, b, c and d are integers greater than or equal to 0, and a+b+c+d≥1, and the flexible peptide segment has a sequence selected from the group consisting of:
 
 (i)
 
 (SEQ ID NO: 6)
 
 GSGGGSGGGGSGGGGS;
 
 
 
 (ii)
 
 (SEQ ID NO: 7)
 
 GSGGGGSGGGGSGGGGSGGGGSGGGGS;
 
 
 
 (iii)
 
 (SEQ ID NO: 8)
 
 GGGGSGGGGSGGGGSGGGGS;
 
 
 
 (iv)
 
 (SEQ ID NO: 9)
 
 GSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS;
 
 and
 
 
 
 (v)
 
 (SEQ ID NO: 10)
 
 GGGSGGGSGGGSGGGSGGGS.